A group of neuroscientists has retracted a paper published earlier this last year in Diabetes after realizing that a figure that took up a whole page of the paper may not have been quite right.

Here’s the notice for “Blockade of receptor for advanced glycation end products in a model of type 1 diabetic leukoencephalopathy”:

The authors have formally requested to retract the above-titled paper, which was published online on 19 November 2012. The authors cite concerns that portions of Fig. 4 were submitted without knowledge of inherent errors or abnormalities that they recognized in retrospect after submission. Therefore, the article has been retracted so the authors can readdress the work and submit it for publication at a later time.

We’ve asked corresponding author Cory Toth, of the University of Calgary, what those errors were, and will update with anything we learn.

While preparing for a subsequent work, it came to our attention that the luxol fast blue images in the image were representative of separate cohorts of mice not studied in the publication. Due to this carelessness, I asked for retraction while we ensured that other images were truly representative and to permit performance of new image acquisition.

In Figure 4G (the pretty red/green images of cells), look in the left panel. About 1/3 of the way from the left, near the top, there’s a trapezoid-shaped cell, looks almost like a red arrow pointing down to the right. Now see if you can spot that exact same shaped cell with its projections, in 3 other places in the left panel. Just for fun, the same cell appears near the bottom right corner of the middle panel, flipped horizontally. Now go look at the left panel again, 1/3 way from the left, near the center, there are 2 cells one above the other (top one has spiny projections). Now take the middle panel and flip it horizontal – see thesame 2 cells again in the same position? The arrow/trapezoid shaped cell also appears in the bottom left. What are the chances of these two images arising from two different genotype animals as claimed in the legend?

well spotted. Also note that figure 4G, right panel has 3 cells that appear similar (one located top middle, one at middle left, and one middle right, all with an orange ‘tail’ and with the same more intense red coloration in the lower part of the cytoplasm). Also check out figure 4B, left panels (the blue panels). Zoom in. Notice any similarities?

“The authors cite concerns that portions of Fig. 4 were submitted without knowledge of inherent errors or abnormalities that they recognized in retrospect after submission.” – this is such an ugly sentence that a politician could spout it. But at least they did not go for “not intentional malfeasance”. Pomposity in writing is used to shield from criticism. Maybe using many words which collectively say very little serves the same purpose.
If what vhedwig says is correct then it is probably not possible to clone a picture within the same figure many times over and be “without knowledge” about it. Unless it was a clerical error or the result of disorganization.

Nice sleuthing vhedwig! As long as we stay away from inflammatory language, we should be OK. Hope you got some sleep Stewart, I saw you were busy this weekend, good job! The are some issues with Supplementary Figure 1B as well. This figure is displaying images from 5 different genotypes, however 1 and 5 looks identical and 2 and 4 looks identical as well. If you play around with contrast, brightness, and saturation etc, you will reveal it in full bloom, especially 2 and 4 since they were cropped differently.

chirality, indeed you are correct. More possibilities: a poor image-archival system, the work of whichever post-doc or graduate student has recently left the lab whose name was omitted from the author list by mistake, or the author who prepared the figure was in a fugue state at the time.

I was going to say that all the bar graphs in Fig. 4 are far too self-similar than you would expect for the size of the error bars shown, but it would take me hours to figure out the chance probability.

I’m confused by the ChAT immunofluorescence in Fig. 4. Are those images supposed to be cortex and/or hippocampus as is implied in the legend? This looks nothing like the ChAT immunoreactivity I see in cortex and hippocampus and more similar to the cells in the basal forbrain that are a main source of acetylcholine.

@Stewart. So far so good, but if some mistake or error happens to pass through the system I will for sure correct the literature immediately. Get some rest you deserve it!
I did some speed sleuthing today and hopefully I find some time to put it together before I go to bed. There are major issues with several papers, so I think this is all on the boss.

This smells fried Canadian bacon.
From the Molecular Pain paper (PMID: 22236461) where Cory Toth (CT) is the last author:
“Authors’ information
CT is the Director of the Neuropathic Pain Clinic, University of Calgary and is a Clinician-Scientist.”

“Authors’ contributions
CT conceived of the study, participated in its design and coordination and drafted the manuscript. CT also performed the surgeries and molecular studies related to the project. JM and MK carried out the delivery of agents and performed behavioral testing in all cases, and performed surgeries for harvesting of tissues. LH and WF participated in study design, assisted in performance of radiolabelled studies, and helped to edit the manuscript. All authors read and approved the final manuscript.”

What we have here is then a PI, who also is a MD and a director of a clinic. The unusual information from the above paper is that CT also did “the surgeries and molecular studies”, which almost wants me to call him Mr Ripley.

The very same paper where the Director made the blots:
Figure 5. Dorsal spinal cord, Intrathecal delivery, CaV-blots, the middle panels of SNL and DPN are identical, just a slight stretch of the height of the SNL panel. The rightmost DPN panel is also identical with the two above, however it it slightly more compressed on the height.
In the same figure, Dorsal spinal cord, Intrathecal delivery, CaV-blots, the rightmost panel’s first two bands are identical to leftmost panel’s two first bands if you flip them vertically and compress them slightly. The rightmost panel has been spliced between the second and third lane.

Two other papers:
Differential impact of diabetes and hypertension in the brain: Adverse effects in grey matter (PMID: 21742034) (the second paper has changed from grey matter to drum-roll… white matter (PMID: 21324363)
Very similar titles is something else similar, why not say identical.

Figure 3E of the grey matter paper is identical to Figure 5D of the white matter paper.

Figure 6A of the grey matter paper: the GSK3B blots for hippocampus and cortex are identical. In general the bands of all the blots in these two paper are very unanchored.

Figure 7A of the grey matter paper: the GSK3B blots for hippocampus and cortex are identical.

Figure 6C. The competition lane of this blot has been pasted in from Figure 7C.

I have to go to bed, but there is a lot more to come. I leave with a first one for me from the lab of Cory Toth. Table 1 of the Brain paper (PMID: 19015157) is identical to Table 1 of the Diabetes paper (PMID: 19136650, both this articles are free you should read the Acknowledgements on this one).

Takes 5 minutes to register a blog. Just make up a nom de guerre email address to do so.
And post away….
If someone really wants to track you and has lots of resources they can – but as others have pointed out, its not too difficult to stay the right side of the libel line (provided you want to that is).

The only thing we know is that CT did the molecular studies according to the authors’ contributions in the Mol Pain paper quoted by me above. Only someone in the lab could answer those questions. He might have done the work, but I would say based on my observations and based on what I’ve heard from other colleagues that a director/physician/PI doing Westerns etc is unheard of. Is he the only one who knows how to do it and/or they have small lab with limited resources? Do you want to have control of the blots to make sure you get the desired results? If you read my follow-up post below on a reply to Marco, I am tempted to speculate that a number of the Western blots (as well as other things, such as the cells vhedwig pointed out) were done once (by CT or someone else in the lab) and then were reused over and over again. Since CT is the PI/corresponding author of most of these studies, he is responsible for the published material and should have noticed that something was/is wrong.

My take on not only these examples below is that they have a set of bands that are reused over and over again (either reuse directly or resize, flip, slightly different angle, change contrast etc). The white backgrounds of many of their blots make this an easy job. Would you call it deliberate, if you flip a band 180 degrees clock wise? Look at B-actin the two C I-I bands, flip the first one 180 degrees clockwise and you end up with the fifth band from left:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661595/figure/F4/
In the same figure there are several examples where you just resize slightly etc you would get identical bands (for example B-Actin, the two D I-I bands and the forth D I-S band).

“Question now is whether many of those taking a look and commenting here have been seeing ghosts.”

I didn’t find Figure 4G that obvious, although I could see similarities. It just seemed that it might be harder to photoshop than actually do the experiment – since that panel doesn’t seem to demonstrate very much. If you take it down to the pixel level the cells identified are not the same – but all kinds of compression issues creep in here since this is a scan of a paper not a high resolution image. Actually the best way to use photoshop (which is the lazy way to fraud) is to print your image out onto paper and then rescan it using a scanner, that ought to confound most forensics. On the other hand Toth’s explanation seemed a bit odd also.

Having said that, I haven’t checked out everything junk science wrote, but I have to concede this
“In the same figure there are several examples where you just resize slightly etc you would get identical bands (for example B-Actin, the two D I-I bands and the forth D I-S band).” amongst others, does look kind of true, if a bit bizarre. You wonder what goes on in his lab if making an actin blot is too much effort.

Perhaps Ivan Oransky could run Toth’s explanation past the editor or also asked if received any complaints before the retraction. If the editor is emphatic s/he received no complaints then maybe Toth is correct, if s/he stonewalls then probably not? Editors may try and without information but they are unlikely to outright lie.

There is an old joke about two Australian politicians John Howard and Andrew Peacock running for the leadership of the opposition party.
John Howard: The thing about Andrew Peacock is he tell you anything you want to hear. If you ask him what day of the week it is, he will say what day of the week do you want it to be? Do you want it to be Tuesday? It can be Tuesday if you like. Now with me, I have no idea what day of the week it is, but I am not going to lie to you about it.

@littlegreyrabbit I hope I can settle the case for you regarding 4G, so one last point, before this post disappears in the flow of all the news that comes out at RW. To do a final illustration of my point about reuse, take a look at Figure 4 (4G to be specific: the leftmost panel as pointed out by Vhedwig above) that the retraction was based upon. The basis for that image is from Figure 5E published in Neurobiol Dis. 2011 Nov;44(2):161-73. (PMID: 21742034). Rotate 5E 180 degrees and add a few cells and voila you will have the leftmost panel of 4G of the Diabetes paper. Totally different experiments of course.

(Note: In the Neurobiol Dis paper the Supplementary Fig. 2 D and F are also the same, rotate, flip and change contrast, saturation. And Supplementary Figure 3 is identical to Supplementary Figure 2 of Neurobiol Dis. 2011 Jun;42(3):446-58. (PMID: 21324363)))

I can confirm the observation from Junk Science regarding figure 4G. It is the same panel with modifications from (PMID: 21742034) Figure 5E. There is absolutely no doubt. Furthermore, Figure 4B contents falsificated data. It can be noted that according to morphological criteria Figure 4B top and middle images from MPB stained slices are taken from the same sample. Maybe they are derived from a different tissue slice or have been digitally modificated, but they are from the same animal and sample. But, according to the results text body and figure legend they should be from different treated groups (Wildtype treated with Placebo vs wildtype DM mice treated with sRAGE). Now the question is: why should the reader believe in the diagramms showing quantitative expression from MAG,MBP and SYP proteins? Why should the reader believe in anything from this study?

Thanks Hans Mueller! You are correct about 4B, there are spots and shapes that make it certain. They just played around with saturation and contrast etc and got two experiments from one picture! 4B is yet another beautiful example of how recycling has gone viral in this lab. Based on the number of papers and figures involved, I hereby denote these “scientists” as serial-frau……
Have you made any plans for your excellent game idea yet?

“@littlegreyrabbit I hope I can settle the case for you regarding 4G, so one last point, before this post disappears in the flow of all the news that comes out at RW. ”

I am sure you are right. I guess what I was trying to say that just based on that image by itself I would have been reluctant to say it was manipulation – however naive that may be. It would be interesting to know what led up to the retraction. And what, if anything, his institution will do.

I understood what you were trying to say and I am also very curious about the bigger picture details. I just wanted to make it clear that this was manipulation, so the people (e.g. RuefulVictim etc) who sometimes doubt the claims made would have no case. I will save your excellent Howard/Peacock joke.

“While preparing for a subsequent work, it came to our attention” – the first part of this sentence attempts to imply that the authors themselves noticed the problems with the figure but the second part implies something quite opposite. This is important and I think the corresponding author knows it. If somebody else let the authors know about the problems with the figure they had spotted in the recently published paper, why on Earth would it matter that it happened when the authors were preparing for subsequent work?

The MBP image is of the posterior forceps of the corpus callosum and the luxol blue is dorsal striatum, corpus callosum (top) and cortical afferent fiber bundles if that helps explain things. I still contend that the density of the ChAT cells is too high for cortex and I’ve never seen somata stained for ChAT in the hippocampus. I will look at some anatomy papers if I have time today.

Aha, the response from the last author explains it all. The pictures in the paper were from some other mice, not the ones in the experiment. And “performance of new image acquisition” is needed. Apparently the authors were not just careless to the extent of grabbing the wrong pictures from their computer. They were careless to the extent of not taking pictures of the experiment when they did it. The cloning of the pictures is therefore not an issue. Carelessness. It’s just carelessness.